Using methodology developed in our group over the last several years to resolve and characterize histone variants, we have been analyzing the patterns of histone synthesis during different cell behavioral states. Histones were found to be synthesized not only during S-phase but also during G1 and the quiescent state (also termed extended G1 or G0). The qualitative pattern of histone synthesis differs between S-phase, G1 and quiescent cells, a finding which shows that the synthesis in G1 or quiescent cells is not due to contamination by S-phase cells. The histone synthesis in both G1 and quiescent cells is not linked to DNA synthesis. Histones synthesized in quiescent cells are stable and seem to be incorporated into chromatin. The results suggest that the quiescent state is not an extended G1 but a discrete state or cycle. Experiments are in progress with histone mRNA's and genes in order to elucidate this phenomenon at the gene level. Histone genes under different kinds of growth control are being isolated and characterized. Using histone synthesis as an indicator of cell state, we are attempting to elucidate some of the mechanisms which control cell cycling and cell proliferation.